This application is designed to provide Michael F. Vaezi, M.D., Ph.D., with a program of mentored, patient-oriented research that will facilitate his development as an independent physician scientist. This proposal outlines a series of studies designed to address the study hypothesis: there is a causal relationship between gastroesophageal reflux disease (GERD) and laryngeal symptoms and signs in patients with laryngitis. This award will allow Dr. Vaezi the unique opportunity to acquire cross-training in clinical design, epidemiology and biostatistics while pursuing a multidisciplinary, patient-oriented research project in better understanding an important clinical area. Laryngoscopic examination of patients with symptoms of hoarseness, sore throat, throat clearing and chronic cough commonly shows laryngeal abnormalities including laryngitis and vocal cord lesions including polyps, granuloma and carcinoma. Gastroesophageal reflux disease often is proposed as the etiology of these abnormalities. However, aggressive acid suppression improves symptoms and laryngeal findings in only some of these patients, highlighting the uncertainty of the relationship between acid reflux and laryngeal pathology. Furthermore, the pathophysiologic role of non-acidic gastric contents in the those whose acid reflux is suppressed with medication is unknown. The advent of new technologic advancement in the field of monitoring acidic and non-acidic reflux in an ambulatory setting will allow Dr. Vaezi to better understand the role of these potential gastric refluxates in causing laryngeal symptoms and injury. Therefore, to better understand the relationship between GERD and laryngeal injury, we propose three in-depth research protocols addressing the following aims: Aim #1: Identify specific laryngoscopic signs associated with GERD. Specific laryngeal signs of gastroesophageal reflux disease will be determined by identifying the signs found in normal subjects and comparing these subjects to reflux patients whose signs improve or resolve with acid-suppressive therapy. In 100 subjects with suspected acid-related laryngeal pathology, the response to aggressive acid suppression with proton pump inhibitors with and without H2-receptor antagonists will be tested with special interest in identifying potential predictors of response, optimum acid-suppressive regimen, dosing and duration of therapy. Aim #2: Identify potential pre-therapy predictors of successful response to GERD related ENT abnormalities. There are currently no data on predictors of response in this group of patients. A major reason for this has been the lack of a large scale trial in which different physiologic tests are performed prior to treatment. In this proposal, in addition to identifying demographic features, we will also perform esophageal manometry, esophageal and hypopharyngeal pH monitoring and multichannel intraluminal impedance (MII) pre- and post-therapy in order to identify potential predictors of successful response. Aim #3: Clarify the role of acidic and non-acidic esophageal reflux in causing laryngeal mucosal injury in patients with ENT complaints. This will be achieved using the state-of-the-art techniques of ambulatory multichannel intraluminal esophageal impedance and pH monitoring. These methods will be employed pre- and post-therapy on all patients to assess their potential clinical utility, especially in those unresponsive to medical therapy after aggressive acid suppression.